It is widely known in the literature that many peptides which act as neurotransmitters in the central nervous system or as releasing factors at the hypothalmic level are characterized by the presence of cyclized glutamic acid (p-GLU) as the NH.sub.2 -terminal amino acid.
For example, neurotensin, a 13 amino acid peptide present in all high order animals, has the initial sequence: p-GLU-LEU-TYR . . . . The releasing factor of the luteinizing hormone is a decapeptide characterized by the initial sequence p-GLU-HIS-TRP . . . . The releasing factor of thyrotropin is a tripeptide of structure p-GLU-HIS-PRO-NH.sub.2. Human gastrin is a 17 amino acid peptide with initial sequence: p-GLU-GLY-PRO . . . . Research on pharmacologically active peptides extracted from amphibian skin or snake venom had led to the interesting discovery that most of these substances are characterized by the presence of p-GLU as NH.sub.2 -terminal amino acid. In effect, physalemin, heledoisin, cerulein, xenopsin, ranatensin, and bombesin are small peptides active at the vasal level with p-GLU as the NH.sub.2 -terminal acid. On the other hand, the work of Ondetti (Biochemistry 10, 4033 (1971)) and Kato (Biochemistry 10, 972 (1971)) identified 15 peptides from snake venom, all with p-GLU as the NH.sub.2 -terminal amino acid. Kato also described (Esperientia 22, 49 (1966)) the presence of tripeptides in some snake venoms: p-GLU-ASN-TRP and p-GLU-GLN-TRP, although no pharmacological activity was mentioned. Even though it is a characteristic common to many pharmacologically active peptides, the presence of p-GLU as NH.sub.2 terminal amino acid has never been correlated with particular physiological effects.